The Distributional Characteristics of Multiple Sclerosis Lesions on Quantitative Susceptibility Mapping and Their Correlation With Clinical Severity

Abstract

Background: Multiple sclerosis (MS) patients have a wide spectrum of severity and responses to therapy; the personalization of treatment relies on sensitive and specific biomarkers. Previous studies have suggested that susceptibility contrast in demyelinated plaques is associated with iron-related pathology in multiple sclerosis which may indicate clinical severity. The aims of this study were to characterize the spatial distribution of MS lesions with different iron patterns by using quantitative susceptibility mapping and to explore neuroradiological findings that correlate with poor clinical outcome.Methods: Twenty-six patients with relapsing–remitting MS [14 men, 12 women; mean age, 29 ± 8 (standard deviation) years; age range, 21–52 years] were included in this study. Differences in lesion number, T2 volume, and susceptibility were compared among lesions subcategorized by location and by the presence or absence of a hyperintense rim on quantitative susceptibility mapping. Associations between these imaging features and clinical outcomes including Expanded Disability Status Scale scores and annual relapse rates were investigated.Results: A total of 811 unifocal MS lesions were included, and their QSM patterns were nodular hyperintensity with no rim (rim–, 540, 67%) or with a hyperintense rim on the edge (rim+, 172, 21%) and nodular isointensity (99, 12%). Rim+ lesions had significantly larger volume (115 ± 142 vs. 166 ± 185 mm3, p < 0.001) and lower susceptibility (4 ± 15 vs. 8 ± 16 ppb, p < 0.05) than rim– lesions. More rim+ lesions were found in periventricular areas [median, 45%; interquartile range (IQR), 36%], whereas a larger proportion of rim– lesions were distributed in juxtacortical (median, 32%; IQR, 21%) and deep white matter (median, 38%; IQR, 22%) areas. The annual relapse rate was positively correlated with the proportion of periventricular rim+ lesions (p < 0.001, r = 0.65) and the proportion of subtentorial rim+ lesions (p < 0.05, r = 0.40). Additionally, a significant association was found between the burden of periventricular rim+ lesions (β = 0.64, p < 0.001) and the burden of subtentorial rim– lesions (β = 0.36, p < 0.05).Conclusions: A high number or lesion burden of periventricular rim+ lesions or subtentorial lesions is associated with frequent clinical relapses.

Magnetic Resonance Imaging in Primary Progressive Multiple Sclerosis Patients

“…[ 72 ], the authors showed that having ≥ 4 rim-positive lesions was associated with motor and cognitive progression in younger patients [ 72 ] and that rim-positive patients had a 3.2-fold higher prevalence of PMS than patients with three or fewer rim-like lesions [ 72 ]. Additionally, a very recently published study showed that the occurrence of rim-positive lesions in periventricular and subtentorial locations was associated with a higher annual relapse rate [ 73 ]. The presence of rim-positive lesions also correlated with higher T2 and T1 lesion volumes and brain atrophy [ 74 ].…”

Quantitative susceptibility mapping in multiple sclerosis: A systematic review and meta-analysis

“…The number of hyperintense QSM lesions in reference to total lesion count on conventional scans (e.g., T2, FLAIR) was most frequently documented. Seventeen studies provided data on the percentages of hyperintense QSM lesions, showing varying proportions that ranged from 13 % to 88 % ( Guo et al, 2021 , Liao et al, 2023 ; Haacke et al, 2021; Castellaro et al, 2017 , Chawla et al, 2016 , Chawla et al, 2018 , Chen et al, 2014 , Cronin et al, 2016 , Gillen et al, 2021 , Harrison et al, 2016 , Kakeda et al, 2015 , Li et al, 2016 , Pelizzari et al, 2020 , Rahmanzadeh et al, 2022 , Tolaymat et al, 2020 , Zhang et al, 2016a , Zhang et al, 2016c ). Additionally, rim lesion counts on QSM were recorded in 12 studies, reporting proportions that ranged from 4 % to 44 % ( Chawla et al, 2018 , Cronin et al, 2016 , Guo et al, 2021 , Gillen et al, 2021 , Li et al, 2016 , Harrison et al, 2016 , Kaunzner et al, 2019 , Huang et al, 2022 , Rahmanzadeh et al, 2022 , Yao et al, 2018 , Zhang et al, 2022 ).…”

“…Abbreviations: Assoc = association, NAWM = normal-appearing white matter, NAGM = normal-appearing grey matter. Clinical and demographical variables in relation to QSM variables Studies with significant results Studies without significant results Proportion of significant findings (%) Reference Assoc Reference Expanded Disease Status Scale Lesion frequency Castellaro et al (2017) + Guo et al (2021) 2/5 (40 %) Tolaymat et al (2020) Haacke et al (2021) Pelizzari et al (2020) Lesion QSM values Coffman et al (2022) + Guo et al (2021) 1/3 (33 %) Harrison et al (2016) Rim lesion frequency Huang et al (2022) + Cronin et al (2016) 4/7 (57 %) Marcille et al (2022) Jang et al (2020) Coffman et al (2022) Yao et al (2018) Tolaymat et al (2020) NAWM QSM values Pietroboni et al (2022) + Pontillo et al (2023) 1/3 (33 %) Hamdy et al (2022) Neurological Assessments Lesion frequency Harrison et al (2016) 0/1 (0 %) Lesion QSM values Harrison et al (2016) 0/1 (0 %) …”

The sequence of regional structural disconnectivity due to multiple sclerosis lesions

“…While the impact of lesion location on disability type/severity has been previously studied in MS 5,31,40 , there are fewer studies that attend to the role of chronic lesion subtype, i.e. chronic active (PRL) vs inactive (non-PRL).…”